Effect of exenatide on peripheral nerve excitability in type 2 diabetes.

OBJECTIVE: To assess the effect of exenatide (a GLP-1 receptor agonist), dipeptidyl peptidase-IV (DPP-IV) inhibitors, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors on measures of peripheral nerve excitability in patients with type 2 diabetes. METHODS: Patients receiving either exenatide (n = 32), a DPP-IV inhibitor (n = 31), or a SGLT-2 inhibitor (n = 27) underwent motor nerve excitability assessments. Groups were similar in age, sex, HbA, diabetes duration, lipids, and neuropathy severity. An additional 10 subjects were assessed prospectively over 3 months while oral anti-hyperglycaemic therapy was kept constant. A cohort of healthy controls (n = 32) were recruited for comparison. RESULTS: Patients receiving a DPP-IV or SGLT-2 inhibitor demonstrated abnormalities in peak threshold reduction, S2 accommodation, superexcitability, and subexcitability. In contrast, patients treated with exenatide were observed to have normal nerve excitability. In the prospective arm, exenatide therapy was associated with an improvement in nerve function as patients demonstrated corrections in S2 accommodation, superexcitability, and subexcitability at follow-up. These changes were independent of the reductions in HbA following exenatide treatment. CONCLUSIONS: Exenatide was associated with an improvement in measures of nerve excitability in patients with type 2 diabetes. SIGNIFICANCE: Exenatide may improve peripheral nerve function in type 2 diabetes.